Abstract

Aims/hypothesis. One subtype of MODY (MODY3) results from the heterozygous mutation of a hepatocyte nuclear factor (HNF)-1!. The pattern of HNF-1! expression in the normal pancreas has not been determined. This study aimed to clarify the profile of HNF-1! protein expression in the developing mouse pancreas.

Methods. Double immunofluorescence staining was carried out for HNF-1! and pancreatic hormones or transcription factors (PDX-1, Pax6, Isl1, and Nkx2.2). The expression of these transcription factors was also studied in the beta cells of HNF-1! mutant mice.

Results. HNF-1! was expressed by both endocrine and exocrine cells of the pancreas. Double immunofluorescence staining showed that HNF-1! was expressed in the nuclei of alpha cells, beta cells, delta cells, and pancreatic polypeptide (PP) cells. HNF-1! was first detected in most pancreatic epithelial cells on embryonic day 10.5 (E10.5), and hormone-positive endocrine cells and amylase-positive cells expressed HNF-1! on E15.5. Most of the Pax6-, Isl1-, or PDX-1-positive cells showed co-expression of HNF-1!. However, HNF-1! immunoreactivity was not observed in 36.0% of Nkx2.2-positive cells. Expression of Nkx2.2, Isl1 and Pax6 seemed to be normal in the beta cells of transgenic mice with dominant negative overexpression of HNF-1!. Expression of PDX-1 did not change in the beta cells of pre-diabetic HNF-1! (-/-) mice, but expression was markedly decreased in the diabetic stage.

Conclusion/interpretation. HNF-1! is expressed by both endocrine cells and exocrine cells of the pancreas from the foetal stage along with other transcription factors, so HNF-1! might play a role during development.